Mycobacteria activate γδ T-cell anti-tumour responses via cytokines from type 1 myeloid dendritic cells: a mechanism of action for cancer immunotherapy

• DOI: 10.1007/s00262-011-1121-4
• Publication Date: 2011-10-14T16:01:08Z
• Authors: Daniel W. Fowler; John Copier; Natalie Wilson; Angus G. Dalgleish; Mark D. Bodman-Smith
• Keywords: Granzyme; Cancer Immunotherapy

Attenuated and heat-killed mycobacteria display demonstrable activity against cancer in the clinic; however, induced immune response is poorly characterised potential biomarkers of ill-defined. We investigated whether three mycobacterial preparations currently used clinic (BCG Mycobacterium vaccae obuense) can stimulate anti-tumour effector responses human γδ T-cells. T-cell were by measuring cytokine production, expression granzyme B cytotoxicity tumour target cells. Results show that T-cells are activated these preparations, as indicated upregulation activation marker proliferation. Activated enhanced responses, shown upregulated expression, production T(H)1 cytokines IFN-γ TNF-α, degranulation to susceptible zoledronic acid-treated resistant Moreover, IL-12, IL-1β TNF-α from circulating type 1 myeloid dendritic cells (DCs), but not 2 DCs or plasmacytoid DCs. Taken together, we BCG, M. obuense induce indirectly via a specific subset suggest mechanism for immunotherapeutic effects cancer.